This application requests five years of funding to establish an Interdisciplinary Behavioral Science Center for Mental Health (IBSC). Our Center builds upon our previous Center for Behavioral Sciences Research and is focused on affective style--consistent individual differences in particular parameters of emotional reactivity and affect regulation. Why some individuals respond especially intensely and persistently to negative events while others appear considerably more resilient, is a question of profound significance to understanding vulnerability to psychopathology. Each of the projects in this Center is focused on different, but related aspects of affective style. Each of the projects converge toward an understanding of the behavioral, neural and hormonal substrates of vulnerability toward mood and anxiety disorders, with a focus on understanding the interconnected roles of different territories of prefrontal cortex, anterior cingulate cortex, amygdala and the hypothalamic-pituitary-adrenal axis (HPA) in these processes. The Center is comprised of five projects and three cores. The projects are focused on different populations including normal adults, adults at putative risk for mood and anxiety disorders based upon biological indices that reflect emotion regulation, adolescents at risk for internalizing disorders, MZ and DZ twin children well-characterized with behavioral and other measures of temperament, and rhesus monkeys also selected to differ on temperamental features that are likely to confer risk for psychopathology. The twin and adolescent samples are tested across multiple projects in both behavioral and MR imaging protocols. There are many common behavioral (supported by a Behavioral Assessment/Clinical Diagnosis Core) and biological measures (supported by a Biological Measures Core that includes MR and microPET imaging, neuroendocrine measures and psychophysiological measures) across the projects. The science proposed will significantly advance our understanding of the neural and behavioral substrates of affective style and this new knowledge will aid in the prediction, prevention and treatment of mood and anxiety disorders.